Seeking A Depersonalization Cure: 5 Treatments For DP/DR

DP/DR or depersonalization/derealization involves a lot of disabling symptoms. Feelings of detachment, emotional numbness, experiencing your life in 3rd person are par for the course.

I've transiently dealt with symptoms of DP/DR and it can be a frightening and disconcerting at best. However, my experience is unusual: DP/DR usually chronic.

DP/DR affects between 1% and 2.4% of the population. If it's so common, why is it assumed to be a rare condition by most clinicians?11

Unfortunately, most psychiatrists are still trained to believe that DPD is extremely rare and that whenever depersonalization is present, it represents an irrelevant symptom stemming from a primary condition such as major depression, an anxiety disorder, or even impending psychosis.

There are a few reasons that psychiatrists might have a harder time identifying DP/DR, but we'll get to that later.

My best guess is that depersonalization is a maladaptive response to stress.

Excessive stress:

  • dysregulates your HPA axis
  • messes with normal vagal tone
  • leads to sustained increases in cortisol.

Too much stress for too long and a cascade of negative effects begins. Your body, ever trying to maintain homeostasis, struggles to adapt to increased stress levels by putting the breaks on emotional reactivity. But in DP/DR, this last step may be an overcorrection.

Researcher Sierra puts it best:

The condition is generated by an anxiety-triggered, ’hard-wired’ inhibitory response to threat.

This down-regulation of stress responsiveness leads to emotional numbing, anhedonia, and detachment. A similar phenomenon is observed in PSTD patients, where they exhibit cortisol levels lower than controls.

By contrast, depressed patients show elevated cortisol and C-reactive protein.

Treatments for Depersonalization

Treatment Dose Authors Results Link
Lamotrigine 25_300 mg/day Aliyev and Aliyev 2011 Statistically significant difference in improvement (i.e., 50% reduction in the CDS) compared placebo
Lamotrigine 25_250 mg/day Sierra et al. 2003 Not better than placebo
Fluoxetine 10_60 mg/day Simeon et al. 2004 Fluoxetine was not demonstrated to be efficacious in treating depersonalisation disorder.
Electro-dermal biofeedback 8 sessions Schoenberg et al. 2012 Electrodermal biofeedback was not effective in increasing SCR (a physiological marker of emotional response) or in decreasing trait measures of depersonalization (CDS)
Naloxone 120 mg/day (average) Simeon et al. 2005 Average 30% reduction of symptoms with treatment, as measured by 3 validated dissociation scales

A number of drug and non-drug treatments have been tested in depersonalization sufferers. However, studies on depersonalization treatment efficacy have been mixed. For example, in one study fluoxetine (Prozac) was not more effective than placebo.

As such, there is no magic bullet for depersonalization. Medications that manipulate serotonin, gluatamate and opioid receptors show promise for treating depersonalization, though results have been inconsistent.

Some commonly proposed treatments include:

  • The anticonvulsant lamotrigine (Lamictal)
  • Opioid antagonists, .e.g, Naloxone
  • Transcranial magnetic stimulation (rTMS) or biofeedback
  • Tricyclic antidepressants like Clomipramine

Clomipramine, lamotrigine, and naloxone have been suggested by researchers as potential treatments for depersonalization disorder. More recently, repetitive transcranial magnetic stimulation (rTMS) is in vogue.

If you think about all the varying states of consciousness that humans can experience, depersonalization is one of the most terrifyingly disconcerting and bizarre. Unfortunately, there's no "gold standard treatment" and finding a medicine or regimen that works may take lots of trial and error.

What is DPDR?

DPDR stands for depersonalization-derealization disorder.

Depersonalization/derealization is a dissociative disorder. Other dissociative disorders include:

  • dissociative amnesia
  • dissociative fugue
  • dissociative identity disorder
  • dissociative disorder not otherwise specified (NOS)

Depersonalization, or derealization, occurs when one feels separated from one's body. It's almost as if you are observing the environment like a detached outsider.

Depersonalization is equally prevalent among men and women and usually occurs without any prior history of identity disorders.

There's overlap between depersonalization and anhedonia or the inability to experience pleasure.

What Triggers Depersonalization?

Depersonalization tends to follow periods of intense anxiety, stress, panic, and depression. DPDR can also be drug-induced (e.g., due to an adverse reaction to hallucinogens).1

The condition usually begins in adolescence and follows a persistent course. It many cases depersonalization produces severe subjective distress and can become incapacitating.

Limbic system suppression in emotional responses has been implicated in depersonalization.

Symptoms of Depersonalization

Patients with depersonalization complain of four symptoms:

  • detachment from their bodies
  • feelings of estrangement from personal memories
  • numbing of emotional responses and dream-like states
  • the feeling that the external world seems unreal2


Depersonalization co-occurs with a variety of other disorders. Depersonalization tends to evade diagnosis due to a high rate of comorbidity.

Some disorders that co-occur with depersonalization include anxiety, depression, borderline personality disorder, and obsessive-compulsive disorder.1

Misdiagnosis of depersonalization may also be high because some psychologists believe it is a secondary effect of other disorders.2

Depersonalization in the context of depression may indicate a marker of resistance to pharmacotherapy.11

Drugs That Treat Depersonalization

Several classes of drugs including amphetamines10, barbiturates, selective serotonin re-uptake inhibitors (SSRIs), and antipsychotics have been tested as treatment options. In several studies, SSRIs have shown some promising effects in treatment. However, findings have been disappointingly inconsistent.2

The visual derealization effect likely arises from changes in the brain’s occipital and temporal circuitry, while symptoms of bodily detachment are attributed to parietal dysfunction.4

Dampened emotional reactivity is linked to inhibition of the amygdala, a component of the limbic system that plays a key role in mediating emotional responses.4

Serotonergic Drugs For Depersonalization

Treatments targeting serotonergic pathways may be viable for depersonalization.

Psilocybin and cannabis have both been found to produce feelings of time distortion and memory impairment.2

The psychoactive effects of cannabis are largely related to activity at cannabinoid receptors. But THC also affects serotonergic pathways. Cannabis-induced depersonalization is dose-dependent. Other marked serotonin agonists such as meta-chlorophenylpiperazine, lysergic acid diethylamide, and ecstasy reportedly elicit depersonalization.

One study administered clomipramine, an SSRI, to eight patients suffering from depersonalization disorder.

After clomipramine treatment, two patients reported drastic improvement in their symptoms. These patients did not have any co-morbid mental illness, such as depression.2 Nevertheless, the singular use of SSRI medication has not been suggested as monotherapy for depersonalization.

Role For Glutamate?

Other research has shown the links between glutamate and depersonalization.


Ketamine, a common anesthetic in veterinary medicine, affects glutamate pathways via NMDA receptor blockade.

Sub-anesthetic doses of ketamine are well known to elicit effects similar to depersonalization. Researchers have investigated this phenomenon with neuroimaging (MRI) and discovered similarities between responses to ketamine and patients with depersonalization 5.

Ketamine releases glutamate after blockade of the NMDA receptors, leading to glutamate’s interaction at other receptor sites.3

Lamictal (Lamotrigine)

Lamotrigine - an anticonvulsant - may mitigate the effects of ketamine-induced depersonalization.

Lamotrigine was given to 32 patients with depersonalization disorder who were also previously prescribed SSRIs. Lamotrogine reduced depersonalization symptoms by over 30% in 18 patients, as measured by the Cambridge Depersonalization Scale.3 One confound of the study was the prior prescription of SSRIs.

Somer et al. note in their meta-analysis that:

Data on lamotrigine for DPRD was inconsistent with one trial indicating that lamotrigine was not significantly better than placebo when applied as a singular treatment for DPRD, and one trial showing a statistically significant difference in improvement (i.e., 50% reduction in the CDS) compared placebo.

Apart from serotonin and glutamate, drugs that target the opioid system have also been tested.

Opioids and Emotional Numbing

The emotional numbing observed in depersonalizaton may be an opioid-mediated phenomenon.

The endogenous opioid system is responsible for mediating pain relief in response to stress. For example, the "runner's high" has been attributed to endogenous opioid like endorphin.

Anxiety and depression are believed to alter the endogenous opioid system.

A particular class of opioid agonists induce effects that are reminiscent of depersonalization. As such, researchers have long speculated that certain opioid antagonists like naloxone may be viable treatments for depersonalization. These assumptions have been born out in clinical studies. High-dose naloxone reduced the effects of long-term depersonalization and border-line personality disorder.4

Naltrexone, another opioid antagonist, was prescribed to 14 patients with depersonalization disorder over a six- or eight-week period. Three patients reported a ~70% reduction in symptoms. A reduction of 30% was reported for the entire group.6

Non-Drug Treatments

Non-pharmacological approaches have been tested for depersonalization.

Repetitive transcranial magnetic stimulation (rTMS) has produced encouraging results. rTMS involves altering the electrical activity of the brain using a magnetic field. A handful of case studies in the late 90s showed promising results after rTMS was used on patients who were refractory to pharmacological treatment.

Seven patients received 20 sessions of rTMS over the course of 10 weeks. One session consisted of TMS at 1 Hz frequency that lasted 15 minutes. TMS was delivered to the ventrolateral prefrontal cortex (VLPFC).

Treatment reduced scores on the Cambridge Depersonalization Scale by 44%, on average. Only one patient failed to respond. The study authors speculated that symptoms might further improve on the Cambridge Depersonalization Scale with more rTMS sessions.

Improvement was also noted on the Beck Depression Inventory and Beck Anxiety Inventory, though the results failed to reach statistical significance.7


Several pharmacological approaches have been tested for the treatment of depersonalization. rTMS is a novel treatment that calls for larger, randomized trials. Though scientists have used rTMS mainly in patients refractory to pharmaceuticals, the treatment shows promise as a first-line approach for alleviating depersonalization.


  1. Simeon D. Depersonalisation disorder: a contemporary overview. CNS Drugs. 2004;18(6):343-54.

  2. Sierra M. Depersonalization disorder: pharmacological approaches. Expert Rev Neurother. 2008;8(1):19-26.

  3. Sierra M, Baker D, Medford N, et al. Lamotrigine as an add-on treatment for depersonalization disorder: a retrospective study of 32 cases. Clin Neuropharmacol. 2006;29(5):253-8.

  4. Dell PF, O'Neil JA. Dissociation and the Dissociative Disorders, DSM-V and Beyond. Taylor & Francis; 2009.

  5. Abel KM, Allin MP, Kucharska-pietura K, et al. Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study. Neuroreport. 2003;14(3):387-91.

  6. Simeon D, Knutelska M. An open trial of naltrexone in the treatment of depersonalization disorder. J Clin Psychopharmacol. 2005;25(3):267-70.

  7. Jay EL, Nestler S, Sierra M, Mcclelland J, Kekic M, David AS. Ventrolateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of depersonalization disorder: A consecutive case series. Psychiatry Res. 2016;240:118-22.

  8. Scarella TM, Franzen JR. Case report: Improvement in dissociative symptoms with mixed amphetamine salts. J Trauma Dissociation. 2016 Nov 14;():1-14

  9. Depersonalization disorder: pharmacological approaches

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Xavier Kent

I'm interested in nutrition, nootropics, and javascript. I'm a firm believer in getting really good at one thing.


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